Once you have selected a great lab, it is time to get to work. How to be successful in that lab is the subject of another essay. But I would advise you to remember a few things. First, do pick an important question but don’t pick the same topic that everyone else is working on. It will be more fun and less competitive to go your own way. For every trendy topic now, there are 100 other topics just as important and hardly studied yet. Second, there is no need to write more than one paper; just make it a good one. It probably will take you about 6 years (counting course work). If you can work on an important question as a PhD student (or postdoc) and take it a step forward, you will have the confidence and enthusiasm to do this for the rest of your life. And students, please, do not skip your postdoctoral fellowship no matter how successful your PhD thesis work has been. It seems to be all the rage these days to shorten training time. NIH is even providing special fellowships for those who want to move directly to independent positions after their PhD training. But I have noticed that people who skip their postdoc may do okay in their own labs, but they generally fail to broaden as scientists or to achieve the versatility and fearlessness to enter new fields that they might otherwise have achieved. That is a large price to pay for skipping what could otherwise be a marvelously fun and rewarding final period of training.